1. Field of Invention
The present invention relates to bio-compound particles and the manufacturing procedure thereof. More particularly, the present invention discloses a calcium phosphate-based bio-compound for use in bone operations and the method of manufacturing the same.
2. Related Art
Bone defects caused due to external forces or other diseases present major difficulties in orthopedic operations. Autogenous bone contains bone morphogenetic proteins and several live bone cells to facilitate recovery of bony tissues and thus become the best choice in bone transplantations. The autogenous bone graft material, however, is obtained from the patient in the operation, and it has the disadvantages that the patient could be infected after the operation and that the amount that can be obtained is very little. Allogenous bone graft, on the other hand, could result in problems such as virus infection (e.g., acquired immune deficiency) and imperfect recovery. Therefore, to facilitate the recovery of bone defects and to prevent the potential problems inherent in autogenous and allogenous transplantations, development in synthetic bone graft substitutes is necessary. The synthetic bone graft substitutes in the state of art cannot be dissolved or resorbed by human bodies, and have inferior properties in handling and moldability. Thus, it is urgent to develop resorbable bone graft substitutes with better handling and moldability to satisfy the needs of bone graft in cranio- and maxillo-facial surgeries, dental applications or orthopedic operations and bone-genesis.
The commercial product Collagraft of the prior art is a compound composed of bioceramics and collagen. However, the weight ratio between collagen and ceramics is very different from that for bony tissues. In spite of the fact that many researches indicate that Collagraft transplanted into animal bodies has good bone-genesis ability, the ceramics contains 60% of hydroxylapatite that cannot be resolved by living tissues.
The techniques disclosed in the U.S. Pat. Nos. 5,658,593 and 5,424,084 describe the methods for preparing such collagen microcapsules.
The network structure of the collagen is the main component of extracellular matrix; thus, collagen microcapsules with a network structure are more similar to living tissues. However, it is not clear from the known techniques disclosed in the patents whether the collagen microcapsules thus formed have a network structure. They also do not reveal any specific processes to form a network structure in the collagen microcapsules. Further, the percentage of collagen in known compounds of collagen and ceramics powders is far less than that in bony tissues.
In view of the foregoing, it is a primary object of the present invention to provide a family of resorbable calcium phosphate-based bio-compound particles, and the manufacturing procedure thereof, to solve problems in the current products in that the synthetic bone graft in the prior art cannot be resolved or absorbed by human bodies, has poor handling or moldability, and is inconvenient to use in clinic applications.
The present invention utilizes the dissolvable, osteo-conductive properties of collagen which can reconstitute into a network structures combines collagen with calcium phosphate-based ceramics powders, such as hydroxylapatite, so that calcium phosphate-based ceramics powders can homogeneously distribute within the reconstituted collagen network structure. In the microscopic structure of bony tissues, bio-apatite is nucleated on the network of osteo-conductive organic materials. In the present invention the compound formed by the calcium phosphate-based ceramics powders and the collagen network structure has a similar microscopic structure to the bony tissues.
Furthermore, the new bone-genesis filling materials prepared by the present invention use resorbable calcium phosphate-based compound particles, the weight ratio of collagen and ceramics powders reaching 35:65, which is similar to bony tissues. The diameters of the ceramics powders are no more than 5 xcexcm; therefore, they can be absorbed by humans. Since the bone filling materials of the present invention have similar components and structures to bony tissues, there is no need for a second operation. They do not only have better handling and moldable properties, but also can fully utilize the re-genesis function of bony tissues to obtain fast and effective bone-genesis.
The resorbable calcium phosphate-based bio-compound prepared by the present invention can be used individually. Another object of the present invention is to, along with the self bone marrows of patients or applying the concept of tissue engineering, make the resorbable calcium phosphate-based bio-compounds prepared thereby the scaffolds of seeded cells and the carriers of relevant growth factors so as to fully utilize the re-genesis function of bony tissues for fast and effective bone-genesis around bone defects.
It is a further object of the present invention to provide a manufacturing technique for making the resorbable calcium phosphate-based bio-compound particles.
Pursuant the above objects, the manufacturing procedure for making the resorbable calcium phosphate-based bio-compound particles provided by the present invention comprises the steps of:
adding homogeneously mingled collagen and hydroxylapatite by droplets into an oil phase so that the collagen-hydroxylapatite mixture has enough time to reconstitute and form particles with a network structure, and obtaining the resorbable calcium phosphate-based bio-compound particle by cross-linking and isolation.